dbSNP rs2638526: KRT8:c.-47+3106C>T (chr12-52946609-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001256293.2(KRT8):c.-47+3106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,982 control chromosomes in the GnomAD database, including 22,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 22388 hom., cov: 31)

Exomes 𝑓: 0.33 ( 0 hom. )

Consequence

KRT8
NM_001256293.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Publications

7 publications found

Variant links:

Genes affected

KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

KRT8 Gene-Disease associations (from GenCC):

cirrhosis, familial
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

KRT8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT8	NM_001256293.2 link	c.-47+3106C>T		intron_variant	Intron 1 of 8		NP_001243222.1	P05787-1
KRT8	NR_045962.2 link	n.405+2847C>T		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
KRT8	ENST00000546897.5 link	c.-47+3106C>T	intron_variant	Intron 1 of 8	2	ENSP00000447402.1	P05787-1
KRT8	ENST00000552551.5 link	c.-47+2847C>T	intron_variant	Intron 1 of 8	2	ENSP00000447566.1	P05787-1
KRT8	ENST00000548998.5 link	c.74+2847C>T	intron_variant	Intron 2 of 6	5	ENSP00000447040.1	F8W1U3

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81037

AN:

151858

Hom.:

22356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.653

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.552

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.523

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.534

AC:

81128

AN:

151976

Hom.:

22388

Cov.:

AF XY:

0.530

AC XY:

39379

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.654

AC:

27086

AN:

41446

American (AMR)

AF:

0.579

AC:

8832

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.552

AC:

1917

AN:

3472

East Asian (EAS)

AF:

0.622

AC:

3210

AN:

5158

South Asian (SAS)

AF:

0.477

AC:

2299

AN:

4820

European-Finnish (FIN)

AF:

0.365

AC:

3858

AN:

10560

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.474

AC:

32224

AN:

67948

Other (OTH)

AF:

0.527

AC:

1113

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1904

3808

5711

7615

9519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.506

Hom.:

36846

Bravo

AF:

0.562

Asia WGS

AF:

0.546

AC:

1898

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.0

(source)

DANN

Benign

0.39

PhyloP100

0.034

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over